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The dual PDZ domain from Postsynaptic density protein 95 forms a scaffold with peptide ligand

DOI: 10.1016/j.bpj.2020.06.018 DOI Help

Authors: N. A. Rodzli (University of Manchester) , M. P. Lockhart-Cairns (University of Manchester) , C. W. Levy (University of Manchester) , J. Chipperfield (University of Manchester) , L. Bird (Wellcome Trust Centre for Human Genetics, University of Oxford) , C. Baldock (University of Manchester) , S. M. Prince (University of Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biophysical Journal

State: Published (Approved)
Published: June 2020

Open Access Open Access

Abstract: PSD-95 is a member of Membrane Associated Guanylate Kinase class of proteins which form scaffolding interactions with partner proteins including ion and receptor channels. PSD-95 is directly implicated in modulating the electrical responses of excitable cells. The first two PSD-95/Disks Large/Zona Occludens (PDZ) domains of PSD-95 have been shown to be the key component in the formation of channel clusters. We report crystal structures of this dual domain in both in apo- and ligand-bound form; thermodynamic analysis of ligand association and Small Angle X-ray Scattering of the dual domain in the absence and presence of ligands. These experiments reveal that the ligated double domain forms a 3-dimensional scaffold which can be described by a Spacegroup. The concentration of the components in this study is comparable to those found in compartments of excitable cells such as the postsynaptic density and juxta-paranodes of Ranvier. These in vitro experiments inform the basis of the scaffolding function of PSD-95 and provide a detailed model for scaffold formation by the PDZ domains of PSD-95.

Journal Keywords: Protein-protein interaction; Biophysical analysis; Clustering; PDZ domain; MAGUK; Scaffold protein

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Other Facilities: P21 at DESY

Documents:
1-s2.0-S000634952030494X-main.pdf

Discipline Tags:

Biophysics Health & Wellbeing Life Sciences & Biotech Neurology Structural biology

Technical Tags:

Diffraction Macromolecular Crystallography (MX) Scattering Small Angle X-ray Scattering (SAXS)